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Full-Text Articles in Genetics and Genomics

Novel Polymorphisms Of Zrsr2 And Gpm6b Gene Homologs And Their Use In Sex Identification Of Bovine And Porcine Species, Evan K. Peterson Dec 2020

Novel Polymorphisms Of Zrsr2 And Gpm6b Gene Homologs And Their Use In Sex Identification Of Bovine And Porcine Species, Evan K. Peterson

All Graduate Theses and Dissertations

Accurate and cost-effective PCR based sex identification is important in animal production because it gives producers the ability to determine the sex of embryos prior to transfer, saving time and money. The most efficient PCR sex identification assays work by using a single primer pair to amplify a specific target region located on the Y-chromosome and a second, separate target region on the X-chromosome.

This thesis reports the design of two novel assays. The first assay was designed to target the Zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2 (ZRSR2) gene found on the X-chromosome and its ...


Molecular Taxonomy And Phylogenetic Analysis Of Dove And Pigeon Species (Aves: Columbidae) Of Pakistan, Based On Coi Region Of Mitochondrial Dna, Hina Rafiq, Fakhar -I-Abbas, Fakhra Nazir, Fida Muhammad Khan Sep 2020

Molecular Taxonomy And Phylogenetic Analysis Of Dove And Pigeon Species (Aves: Columbidae) Of Pakistan, Based On Coi Region Of Mitochondrial Dna, Hina Rafiq, Fakhar -I-Abbas, Fakhra Nazir, Fida Muhammad Khan

Journal of Bioresource Management

Doves and Pigeons are the members of living family Columbidae (Order: Columbiformes) having a wide range of taxonomic diversity and geographic distribution. Seven species with one sample each of family Columbidae were collected via random sampling from different districts of Pakistan to carry out this study. The targeted gene region was sequenced and identified by using BLAST tool at National Center for Biotechnology Information (NCBI). CLUSTALW was used for sequence alignment and MEGA6 for reconstruction of phylogenetic trees to predict the effective ancestry of different Columbidae species. The following phylogenetic trees were obtained i.e. Maximum Likelihood tree, Neighborhood joining ...


Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan Sep 2020

Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan

Biochemistry Publications

Purpose: Inhomogeneous exposures to ionizing radiation can be detected and quantified with the Dicentric Chromosome Assay (DCA) of metaphase cells. Complete automation of interpretation of the DCA for whole body irradiation has significantly improved throughput without compromising accuracy, however low levels of residual false positive dicentric chromosomes (DCs) have confounded its application for partial body exposure determination.

Materials and Methods: We describe a method of estimating and correcting for false positive DCs in digitally processed images of metaphase cells. Nearly all DCs detected in unirradiated calibration samples are introduced by digital image processing. DC frequencies of irradiated calibration samples and ...


Whole Genome Sequence Data Provides Novel Insights Into The Genetic Architecture Of Meat Quality Traits In Beef, Joel D. Leal-Gutiérrez, Fernanda M. Rezende, James M. Reecy, Luke M. Kramer, Francisco Peñagaricano, Raluca G. Mateescu Sep 2020

Whole Genome Sequence Data Provides Novel Insights Into The Genetic Architecture Of Meat Quality Traits In Beef, Joel D. Leal-Gutiérrez, Fernanda M. Rezende, James M. Reecy, Luke M. Kramer, Francisco Peñagaricano, Raluca G. Mateescu

Animal Science Publications

Tenderness is a major quality attribute for fresh beef steaks in the United States, and meat quality traits in general are suitable candidates for genomic research. The objectives of the present analysis were to (1) perform genome-wide association (GWA) analysis for marbling, Warner-Bratzler shear force (WBSF), tenderness, and connective tissue using whole-genome data in an Angus population, (2) identify enriched pathways in each GWA analysis; (3) construct a protein–protein interaction network using the associated genes and (4) perform a μ-calpain proteolysis assessment for associated structural proteins. An Angus-sired population of 2,285 individuals was assessed. Animals were transported to ...


Pfred: A Computational Platform For Sirna And Antisense Oligonucleotides Design, Simone Sciabola, Hualin Xi, Dario Cruz, Qing Cao, Christine Lawrence, Tianhong Zhang, Sergio Rotstein, Jason D. Hughes, Daniel R. Caffrey, Robert Stanton Aug 2020

Pfred: A Computational Platform For Sirna And Antisense Oligonucleotides Design, Simone Sciabola, Hualin Xi, Dario Cruz, Qing Cao, Christine Lawrence, Tianhong Zhang, Sergio Rotstein, Jason D. Hughes, Daniel R. Caffrey, Robert Stanton

University of Massachusetts Medical School Faculty Publications

PFRED a software application for the design, analysis, and visualization of antisense oligonucleotides and siRNA is described. The software provides an intuitive user-interface for scientists to design a library of siRNA or antisense oligonucleotides that target a specific gene of interest. Moreover, the tool facilitates the incorporation of various design criteria that have been shown to be important for stability and potency. PFRED has been made available as an open-source project so the code can be easily modified to address the future needs of the oligonucleotide research community. A compiled version is available for downloading at https://github.com/pfred ...


Phylogenetic Analysis Of Sars-Cov-2 In The Boston Area Highlights The Role Of Recurrent Importation And Superspreading Events, Jacob Lemieux, Katherine J. Siddle, Jeremy Luban, Glen R. Gallagher, Lawrence C. Madoff, Sandra Smole, Virginia M. Pierce, Eric Rosenberg, Pardis C. Sabeti, Daniel J. Park, Bronwyn L. Macinnis Aug 2020

Phylogenetic Analysis Of Sars-Cov-2 In The Boston Area Highlights The Role Of Recurrent Importation And Superspreading Events, Jacob Lemieux, Katherine J. Siddle, Jeremy Luban, Glen R. Gallagher, Lawrence C. Madoff, Sandra Smole, Virginia M. Pierce, Eric Rosenberg, Pardis C. Sabeti, Daniel J. Park, Bronwyn L. Macinnis

COVID-19 Publications by UMMS Authors

SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region, including nearly all confirmed cases within the first week of the epidemic and hundreds of cases from major outbreaks at a conference, a nursing facility, and among homeless shelter guests and staff. The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe ...


Genome-Wide Mapping Of Human Dna Replication By Optical Replication Mapping Supports A Stochastic Model Of Eukaryotic Replication Timing, Weitao Wang, Kyle Klein, Karel Proesmans, Northwestern University, Claire Marchal, Xiaopeng Zhu, Tyler M. Borrman, Alex Hastie, Zhiping Weng, Simon Fraser University, Paris Sciences Et Lettres University, Florida State University, Nicholas R. Rhind Aug 2020

Genome-Wide Mapping Of Human Dna Replication By Optical Replication Mapping Supports A Stochastic Model Of Eukaryotic Replication Timing, Weitao Wang, Kyle Klein, Karel Proesmans, Northwestern University, Claire Marchal, Xiaopeng Zhu, Tyler M. Borrman, Alex Hastie, Zhiping Weng, Simon Fraser University, Paris Sciences Et Lettres University, Florida State University, Nicholas R. Rhind

University of Massachusetts Medical School Faculty Publications

DNA replication is regulated by the location and timing of replication initiation. Therefore, much effort has been invested in identifying and analyzing the sites of human replication initiation. However, the heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual initiation site utilization in metazoans has made mapping the location and timing of replication initiation in human cells difficult. A potential solution to the problem of human replication mapping is single-molecule analysis. However, current approaches do not provide the throughput required for genome-wide experiments. To address this challenge, we have developed Optical Replication Mapping (ORM), a high-throughput single-molecule ...


Genome-Wide Characterization Of The Grf Family And Their Roles In Response To Salt Stress In Gossypium, Jun-Feng Cao, Jin-Quan Huang, Xia Liu, Chao-Chen Huang, Zi-Shou Zheng, Xiu-Fang Zhang, Xiao-Xia Shangguan, Ling-Jian Wang, Yu-Gao Zhang, Jonathan F. Wendel, Corrinne E. Grover, Zhi-Wen Chen Aug 2020

Genome-Wide Characterization Of The Grf Family And Their Roles In Response To Salt Stress In Gossypium, Jun-Feng Cao, Jin-Quan Huang, Xia Liu, Chao-Chen Huang, Zi-Shou Zheng, Xiu-Fang Zhang, Xiao-Xia Shangguan, Ling-Jian Wang, Yu-Gao Zhang, Jonathan F. Wendel, Corrinne E. Grover, Zhi-Wen Chen

Ecology, Evolution and Organismal Biology Publications

Background: Cotton (Gossypium spp.) is the most important world-wide fiber crop but salt stress limits cotton production in coastal and other areas. Growth regulation factors (GRFs) play regulatory roles in response to salt stress, but their roles have not been studied in cotton under salt stress.

Results: We identified 19 GRF genes in G. raimondii, 18 in G. arboreum, 34 in G. hirsutum and 45 in G. barbadense, respectively. These GRF genes were phylogenetically analyzed leading to the recognition of seven GRF clades. GRF genes from diploid cottons (G. raimondii and G. arboreum) were largely retained in allopolyploid cotton, with ...


Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin Aug 2020

Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin

COVID-19 Publications by UMMS Authors

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike ...


From Phocine Distemper To Avian Influenza: A Study Of Immunogenetic Diversity In Two Sympatric Pinniped Species, Alayna K. Gigliotti Aug 2020

From Phocine Distemper To Avian Influenza: A Study Of Immunogenetic Diversity In Two Sympatric Pinniped Species, Alayna K. Gigliotti

Electronic Theses and Dissertations

Gray (Halichoerus grypus) and harbor (Phoca vitulina) seals are sympatric species that inhabit the North Atlantic and have been subject to mortality events from disease outbreaks, particularly phocine distemper and avian influenza virus. Across mortality events, gray seals tend to exhibit a higher survival rate, which could be explained by various ecological factors impacting rates or direction of selection in parts of the genome related to the immune system. These factors could include haul-out site density, habitat, and degree of inter/intraspecies interaction. This research aims to compare genetic diversity within the Major Histocompatibility Complex (MHC) class I gene complex ...


Rates And Patterns Of Indels In Hiv-1 Gp120 Within And Among Hosts, John Lawrence Palmer Aug 2020

Rates And Patterns Of Indels In Hiv-1 Gp120 Within And Among Hosts, John Lawrence Palmer

Electronic Thesis and Dissertation Repository

Insertions and deletions (indels) in the HIV-1 gp120 variable loops modulate sensitivity to neutralizing antibodies and are therefore implicated in HIV-1 immune escape. However, the rates and characteristics of variable loop indels have not been investigated within hosts. Here, I report a within-host phylogenetic analysis of gp120 variable loop indels, with mentions to my preceding study on these indels among hosts.

We processed longitudinally-sampled gp120 sequences collected from a public database (n = 11,265) and the Novitsky Lab (n=2,541). I generated time-scaled within-host phylogenies using BEAST, extracted indels by reconstructing ancestral sequences in Historian, and estimated variable loop ...


Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Toward Goblet Cell Lineage In The Mouse Intestine, Joyce H. Li, Subir Ray, Alper Kucukural, Gerard Gradwohl, Andrew B. Leiter Aug 2020

Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Toward Goblet Cell Lineage In The Mouse Intestine, Joyce H. Li, Subir Ray, Alper Kucukural, Gerard Gradwohl, Andrew B. Leiter

University of Massachusetts Medical School Faculty Publications

BACKGROUND and AIMS: Transient expression of Neurog3 commits intestinal secretory progenitors to become enteroendocrine-biased progenitors and hence drive enteroendocrine differentiation. Loss of Neurog3 in mouse resulted in the depletion of intestinal enteroendocrine cells (EECs) and an increase in goblet cells. Earlier studies in developing mouse pancreas showed Neurog3 gene dosage in endocrine and exocrine cell fate allocation. We aimed to determine whether Neurog3 gene dosage controls fate choice of enteroendocrine progenitors.

METHODS: We acquired mutant Neurog3 reporter mice carrying 2, 1, or null Neurog3 alleles to study Neurog3 gene dosage effect by lineage tracing. Cell types arising from Neurog3+ progenitors ...


Inherent Regulatory Asymmetry Emanating From Network Architecture In A Prevalent Autoregulatory Motif, Zulfikar Ali, Vinuselvi Parisutham, Sandeep Choubey, Robert C. Brewster Aug 2020

Inherent Regulatory Asymmetry Emanating From Network Architecture In A Prevalent Autoregulatory Motif, Zulfikar Ali, Vinuselvi Parisutham, Sandeep Choubey, Robert C. Brewster

Open Access Articles

Predicting gene expression from DNA sequence remains a major goal in the field of gene regulation. A challenge to this goal is the connectivity of the network, whose role in altering gene expression remains unclear. Here, we study a common autoregulatory network motif, the negative single-input module, to explore the regulatory properties inherited from the motif. Using stochastic simulations and a synthetic biology approach in E. coli, we find that the TF gene and its target genes have inherent asymmetry in regulation, even when their promoters are identical; the TF gene being more repressed than its targets. The magnitude of ...


The P-Glycoprotein Repertoire Of The Equine Parasitic Nematode Parascaris Univalens, Alexander P. Gerhard, Jürgen Krücken, Emanuel Heitlinger, I. Jana I. Janssen, Marta Basiaga, Sławomir Kornaś, Céline Beier, Martin K. Nielsen, Richard E. Davis, Jianbin Wang, Georg Von Samson-Himmelstjerna Aug 2020

The P-Glycoprotein Repertoire Of The Equine Parasitic Nematode Parascaris Univalens, Alexander P. Gerhard, Jürgen Krücken, Emanuel Heitlinger, I. Jana I. Janssen, Marta Basiaga, Sławomir Kornaś, Céline Beier, Martin K. Nielsen, Richard E. Davis, Jianbin Wang, Georg Von Samson-Himmelstjerna

Maxwell H. Gluck Equine Research Center Faculty Publications

P-glycoproteins (Pgp) have been proposed as contributors to the widespread macrocyclic lactone (ML) resistance in several nematode species including a major pathogen of foals, Parascaris univalens. Using new and available RNA-seq data, ten different genomic loci encoding Pgps were identified and characterized by transcriptome-guided RT-PCRs and Sanger sequencing. Phylogenetic analysis revealed an ascarid-specific Pgp lineage, Pgp-18, as well as two paralogues of Pgp-11 and Pgp-16. Comparative gene expression analyses in P. univalens and Caenorhabditis elegans show that the intestine is the major site of expression but individual gene expression patterns were not conserved between the two nematodes. In P. univalens ...


A Shark Conservationists Toolbox: Current Dna Methods And Techniques Aiding In The Conservation Of Sharks, Arianna N. Nixon Aug 2020

A Shark Conservationists Toolbox: Current Dna Methods And Techniques Aiding In The Conservation Of Sharks, Arianna N. Nixon

All HCAS Student Capstones, Theses, and Dissertations

Elasmobranchs are important members of their community. Many sharks are important apex predators that help maintain the health of their ecosystem. However, shark populations are globally declining. This is partially due to the fact that sharks are highly targeted for their fins, meat, liver oil, teeth, and skin. However, they are also killed from anthropogenic effects such as habitat destruction and pollution. Most shark species have life history characteristics that also make them more vulnerable to overfishing. Sharks are also difficult to study due to their elusive nature and identification issues. That is why molecular tools are increasingly becoming important ...


Transcriptome Analysis Reveals Inhibitory Effects Of Lentogenic Newcastle Disease Virus On Cell Survival And Immune Function In Spleen Of Commercial Layer Chicks, Jibin Zhang, Michael G. Kaiser, Rodrigo A. Gallardo, Terra R. Kelly, Jack C. M. Dekkers, Huaijun Zhou, Susan J. Lamont Aug 2020

Transcriptome Analysis Reveals Inhibitory Effects Of Lentogenic Newcastle Disease Virus On Cell Survival And Immune Function In Spleen Of Commercial Layer Chicks, Jibin Zhang, Michael G. Kaiser, Rodrigo A. Gallardo, Terra R. Kelly, Jack C. M. Dekkers, Huaijun Zhou, Susan J. Lamont

Animal Science Publications

As a major infectious disease in chickens, Newcastle disease causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 dpi after infection at day21 with a lentogenic Newcastle disease virus in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV challenged and nonchallenged groups, 526 differentially expressed genes (DEGs) (FDR < 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, IPA analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis and angiogenesis. Upregulation of Interferon Induced Protein with Tetratricopeptide Repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK Signaling Antagonist 1 (SPRY1), a DEG in the current study is located in a significant QTL associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.


Melting Dsdna Donor Molecules Potentiates Precision Genome Editing In C. Elegans, Krishna S. Ghanta, Craig C. Mello Aug 2020

Melting Dsdna Donor Molecules Potentiates Precision Genome Editing In C. Elegans, Krishna S. Ghanta, Craig C. Mello

University of Massachusetts Medical School Faculty Publications

CRISPR genome editing has revolutionized genetics in many organisms. In the nematode Caenorhabditis elegans one injection into each of the two gonad arms of an adult hermaphrodite exposes hundreds of meiotic germ cells to editing mixtures, permitting the recovery of multiple indels or small precision edits from each successfully injected animal. Unfortunately, particularly for long insertions, editing efficiencies can vary widely, necessitating multiple injections, and often requiring co-selection strategies. Here we show that melting double stranded DNA (dsDNA) donor molecules prior to injection increases the frequency of precise homology-directed repair (HDR) by several fold for longer edits. We describe troubleshooting ...


Brainstem Ischemic Syndrome In Juvenile Nf2., John W Henson, Tara Benkers, Connor Mccormick Aug 2020

Brainstem Ischemic Syndrome In Juvenile Nf2., John W Henson, Tara Benkers, Connor Mccormick

Articles, Abstracts, and Reports

Objective: A new case of brainstem ischemic necrosis in a young woman with de novo neurofibromatosis type 2 (NF2) is reported, and given notable similarities to 7 prior cases of brainstem stroke in the literature, features defining a possible syndrome were sought.

Methods: Case review including detailed clinical assessment, neuroimaging analysis, genetic testing, and brain biopsy, followed by a multicase analysis.

Results: Brainstem ischemia in juvenile NF2 typically occurs in teenagers without previously known NF2 as an acute, monophasic presentation with restricted diffusion in the midbrain or pons following a recent hypoperfusion event, normal vascular imaging, obvious intracranial imaging features ...


Conservation And Divergence In Duplicated Fiber Coexpression Networks Accompanying Domestication Of The Polyploid Gossypium Hirsutum L, Joseph P. Gallagher, Corrinne E. Grover, Guanjing Hu, Josef J. Jareczek, Jonathan F. Wendel Aug 2020

Conservation And Divergence In Duplicated Fiber Coexpression Networks Accompanying Domestication Of The Polyploid Gossypium Hirsutum L, Joseph P. Gallagher, Corrinne E. Grover, Guanjing Hu, Josef J. Jareczek, Jonathan F. Wendel

Ecology, Evolution and Organismal Biology Publications

Gossypium hirsutum L. (Upland cotton) has an evolutionary history involving inter-genomic hybridization, polyploidization, and subsequent domestication. We analyzed the developmental dynamics of the cotton fiber transcriptome accompanying domestication using gene coexpression networks for both joint and homoeologous networks. Remarkably, most genes exhibited expression for at least one homoeolog, confirming previous reports of widespread gene usage in cotton fibers. Most coexpression modules comprising the joint network are preserved in each subgenomic network and are enriched for similar biological processes, showing a general preservation of network modular structure for the two co-resident genomes in the polyploid. Interestingly, only one fifth of homoeologs ...


Model-Based Analysis Of Chromatin Interactions From Dcas9-Based Capture-3c-Seq., Yong Chen, Yunfei Wang, Xin Liu, Jian Xu, Michael Q Zhang Jul 2020

Model-Based Analysis Of Chromatin Interactions From Dcas9-Based Capture-3c-Seq., Yong Chen, Yunfei Wang, Xin Liu, Jian Xu, Michael Q Zhang

Faculty Scholarship for the College of Science & Mathematics

Deciphering long-range chromatin interactions is critical for understanding temporal and tissue-specific gene expression regulated by cis- and trans-acting factors. By combining the chromosome conformation capture (3C) and biotinylated dCas9 system, we previously established a method CAPTURE-3C-seq to unbiasedly identify high-resolution and locus-specific long-range DNA interactions. Here we present the statistical model and a flexible pipeline, C3S, for analysing CAPTURE-3C-seq or similar experimental data from raw sequencing reads to significantly interacting chromatin loci. C3S provides all steps for data processing, quality control and result illustration. It can automatically define the bin size based on the binding peak of the dCas9-targeted regions ...


An Atlas Of Cell Types In The Mouse Epididymis And Vas Deferens, Vera D. Rinaldi, Elisa Donnard, Kyle Gellatly, Morten Rasmussen, Alper Kucukural, Onur Yukselen, Manuel Garber, Upasna Sharma, Oliver J. Rando Jul 2020

An Atlas Of Cell Types In The Mouse Epididymis And Vas Deferens, Vera D. Rinaldi, Elisa Donnard, Kyle Gellatly, Morten Rasmussen, Alper Kucukural, Onur Yukselen, Manuel Garber, Upasna Sharma, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

Following testicular spermatogenesis, mammalian sperm continue to mature in a long epithelial tube known as the epididymis, which plays key roles in remodeling sperm protein, lipid, and RNA composition. To understand the roles for the epididymis in reproductive biology, we generated a single-cell atlas of the murine epididymis and vas deferens. We recovered key epithelial cell types including principal cells, clear cells, and basal cells, along with associated support cells that include fibroblasts, smooth muscle, macrophages and other immune cells. Moreover, our data illuminate extensive regional specialization of principal cell populations across the length of the epididymis. In addition to ...


Aspen Next Generation: Conversations From Southern Colorado And Northern New Mexico, Dan Binkley, Bill Romme Jul 2020

Aspen Next Generation: Conversations From Southern Colorado And Northern New Mexico, Dan Binkley, Bill Romme

Aspen Bibliography

Aspen trees and forests are especially important in the Rocky Mountains. Aspens add beauty to landscapes, foster high diversity and productivity of understory plants, provide for the habitat needs of many species of animals, and moderate fire behavior. There is a perception that aspen trees and stands are not regenerating well in southern Colorado and northern New Mexico; cohorts of trees younger than a few decades are scarce, at least in some areas. The next generation of aspen in the southern Rockies will be influenced by land use decisions, including harvesting, fire policy and management, and browsing by livestock and ...


Building The Interphase Nucleus: A Study On The Kinetics Of 3d Chromosome Formation, Temporal Relation To Active Transcription, And The Role Of Nuclear Rnas, Kristin N. Abramo Jul 2020

Building The Interphase Nucleus: A Study On The Kinetics Of 3d Chromosome Formation, Temporal Relation To Active Transcription, And The Role Of Nuclear Rnas, Kristin N. Abramo

GSBS Dissertations and Theses

Following the discovery of the one-dimensional sequence of human DNA, much focus has been directed on microscopy and molecular techniques to learn about the spatial organization of chromatin in a 3D cell. The development of these powerful tools has enabled high-resolution, genome-wide analysis of chromosome structure under many different conditions. In this thesis, I focus on how the organization of interphase chromatin is established and maintained following mitosis. Mitotic chromosomes are folded into helical loop arrays creating short and condensed chromosomes, while interphase chromosomes are decondensed and folded into a number of structures at different length scales ranging from loops ...


Beaver And Naked Mole Rat Genomes Reveal Common Paths To Longevity, Xuming Zhou, Elinor K. Karlsson, Vadim N. Gladyshev Jul 2020

Beaver And Naked Mole Rat Genomes Reveal Common Paths To Longevity, Xuming Zhou, Elinor K. Karlsson, Vadim N. Gladyshev

University of Massachusetts Medical School Faculty Publications

Long-lived rodents have become an attractive model for the studies on aging. To understand evolutionary paths to long life, we prepare chromosome-level genome assemblies of the two longest-lived rodents, Canadian beaver (Castor canadensis) and naked mole rat (NMR, Heterocephalus glaber), which were scaffolded with in vitro proximity ligation and chromosome conformation capture data and complemented with long-read sequencing. Our comparative genomic analyses reveal that amino acid substitutions at "disease-causing" sites are widespread in the rodent genomes and that identical substitutions in long-lived rodents are associated with common adaptive phenotypes, e.g., enhanced resistance to DNA damage and cellular stress. By ...


Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König Jul 2020

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution ...


Insights From Population Genomics To Enhance And Sustain Biological Control Of Insect Pests, Arun Sethuraman, Fredric J. Janzen, David W. Weisrock, John J. Obrycki Jul 2020

Insights From Population Genomics To Enhance And Sustain Biological Control Of Insect Pests, Arun Sethuraman, Fredric J. Janzen, David W. Weisrock, John J. Obrycki

Ecology, Evolution and Organismal Biology Publications

Biological control—the use of organisms (e.g., nematodes, arthropods, bacteria, fungi, viruses) for the suppression of insect pest species—is a well-established, ecologically sound and economically profitable tactic for crop protection. This approach has served as a sustainable solution for many insect pest problems for over a century in North America. However, all pest management tactics have associated risks. Specifically, the ecological non-target effects of biological control have been examined in numerous systems. In contrast, the need to understand the short- and long-term evolutionary consequences of human-mediated manipulation of biological control organisms for importation, augmentation and conservation biological control ...


Simultaneous Epigenetic Perturbation And Genome Imaging Reveal Distinct Roles Of H3k9me3 In Chromatin Architecture And Transcription, Ying Feng, Yao Wang, Xiangnan Wang, Xiaohui He, Chen Yang, Ardalan Naseri, Thoru Pederson, Jing Zheng, Shaojie Zhang, Xiao Xiao, Wei Xie, Hanhui Ma Jul 2020

Simultaneous Epigenetic Perturbation And Genome Imaging Reveal Distinct Roles Of H3k9me3 In Chromatin Architecture And Transcription, Ying Feng, Yao Wang, Xiangnan Wang, Xiaohui He, Chen Yang, Ardalan Naseri, Thoru Pederson, Jing Zheng, Shaojie Zhang, Xiao Xiao, Wei Xie, Hanhui Ma

University of Massachusetts Medical School Faculty Publications

Despite the long-observed correlation between H3K9me3, chromatin architecture and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Here we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread ...


Meta-Analysis Of The Alzheimer's Disease Human Brain Transcriptome And Functional Dissection In Mouse Models., Ying-Wooi Wan, Rami Al-Ouran, Carl G Mangleburg, Thanneer M Perumal, Tom V Lee, Katherine Allison, Vivek Swarup, Cory C Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M Neuner, Catherine C Kaczorowski, Vivek M Philip, Gareth R Howell, Heidi Martini-Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Michelle E Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K Sieberts, Larsson Omberg, Kristen D Dang, James A Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Winston Hide, Christoph Preuss, Ayla Ergun, Phillip J Ebert, David C Airey, Sara Mostafavi, Lei Yu, Hans-Ulrich Klein, Accelerating Medicines Partnership, Alzheimer’S Disease Consortium, Gregory W Carter, David A Collier, Todd E Golde, Allan I Levey, David A Bennett, Karol Estrada, T Matthew Townsend, Bin Zhang, Eric Schadt, Philip L De Jager, Nathan D Price, Nilüfer Ertekin-Taner, Zhandong Liu, Joshua M Shulman, Lara M Mangravite, Benjamin A Logsdon Jul 2020

Meta-Analysis Of The Alzheimer's Disease Human Brain Transcriptome And Functional Dissection In Mouse Models., Ying-Wooi Wan, Rami Al-Ouran, Carl G Mangleburg, Thanneer M Perumal, Tom V Lee, Katherine Allison, Vivek Swarup, Cory C Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M Neuner, Catherine C Kaczorowski, Vivek M Philip, Gareth R Howell, Heidi Martini-Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Michelle E Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K Sieberts, Larsson Omberg, Kristen D Dang, James A Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Winston Hide, Christoph Preuss, Ayla Ergun, Phillip J Ebert, David C Airey, Sara Mostafavi, Lei Yu, Hans-Ulrich Klein, Accelerating Medicines Partnership, Alzheimer’S Disease Consortium, Gregory W Carter, David A Collier, Todd E Golde, Allan I Levey, David A Bennett, Karol Estrada, T Matthew Townsend, Bin Zhang, Eric Schadt, Philip L De Jager, Nathan D Price, Nilüfer Ertekin-Taner, Zhandong Liu, Joshua M Shulman, Lara M Mangravite, Benjamin A Logsdon

Articles, Abstracts, and Reports

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD ...


Anti-Crispr Proteins: Applications In Genome Engineering, Jooyoung Lee Jul 2020

Anti-Crispr Proteins: Applications In Genome Engineering, Jooyoung Lee

GSBS Dissertations and Theses

Clustered, regularly interspaced, short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) constitute a bacterial and archaeal adaptive immune system. The ongoing arms race between prokaryotic hosts and their invaders such as phages led to the emergence of anti-CRISPR proteins as countermeasures against the potent antiviral defense. Since the first examples of anti-CRISPRs were shown in a subset of CRISPR-Cas systems, we endeavored to uncover these naturally-occurring inhibitors that inactivate different types of CRISPR-Cas systems. In the first part of my thesis, we have identified and characterized Type II anti-CRISPR proteins that inactivate several Cas9 orthologs. We share mechanistic insights into anti-CRISPR ...


Inter-Tumor Heterogeneity-Melanomas Respond Differently To Gm-Csf-Mediated Activation., Adi Moshe, Sivan Izraely, Orit Sagi-Assif, Sapir Malka, Shlomit Ben-Menachem, Tsipi Meshel, Metsada Pasmanik-Chor, Dave Hoon, Isaac P Witz Jul 2020

Inter-Tumor Heterogeneity-Melanomas Respond Differently To Gm-Csf-Mediated Activation., Adi Moshe, Sivan Izraely, Orit Sagi-Assif, Sapir Malka, Shlomit Ben-Menachem, Tsipi Meshel, Metsada Pasmanik-Chor, Dave Hoon, Isaac P Witz

Articles, Abstracts, and Reports

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo ...